Jane Lee Hoover-Plow Ph.D.

Associate Staff

  • Department of Molecular Cardiology
  • Lerner Research Institute / NB50
  • 9500 Euclid Avenue
  • Cleveland, Ohio 44195
  • hooverj@ccf.org
  • (216) 445-8207
  • (216) 444-8204

Our goal is to determine the mechanisms by which plasminogen (Plg) regulates leukocyte migration and, thereby, the inflammatory responses that contribute to thrombosis and cardiovascular diseases. Our results suggest that leukocyte recruitment to sites of inflammation is dependent on Plg activation of metalloproteinase-9, a matrix degrading enzyme. Lp(a) is an independent risk factor for cardiovascular diseases, but the mechanism of its proarteriothrombotic role is not known. Lp(a) contains an LDL core, plus apolipoprotein(a), that mimics the functions of Plg. In mouse models of inflammation, we found apo(a) reduces neutrophil recruitment, independent of Plg, and reduces macrophage recruitment by inhibiting Plg. In addition to leukocytes, Plg also regulates stem cell recruitment, which is important for the recovery of a myocardial infaraction.

Recently, we demonstrated a novel pathway induced by G-CSF of Plg-dependent stem cell mobilization from the bone marrow that requires MMP-9 activation and regulation of the SDF-1/CXCR-4 pathway, and that this Plg-dependent pathway is important for cardiac repair after an MI.

Strategies to prevent thrombosis have lagged far behind due to, in part, the contribution of multiple and as yet undefined genetic factors that lead to thrombotic risk. In a region on mouse chromosome 17 that is homologous to a region in humans, we identified a candidate gene, EMILIN2, as a thrombosis modifier. EMILIN2, an extracellular matrix protein, is expressed in bone marrow and platelets and plays a role in the platelet function.  

In other words ...

Cardiovascular disease is the leading cause of death in the United States. Our research investigates how cells are recruited to the sites of heart and blood vessel injury and contribute to the progression of disease and influence recovery. 

  • Jessica Grondolsky
  • Animal Husbandry Technician
  • Location:NB5-118
  • Phone:(216) 445-6639
  • brownj3@ccf.org

HIGHLIGHTED PUBLICATIONS

  1. Plasminogen regulates cardiac repair after myocardial infarction through its noncanonical function in stem cell homing to the infarcted heart. Gong Y, Zhao Y, Li Y, Fan Y, Hoover-Plow J.  J Am Coll Cardiol. 2014 Jul 1;63(25 Pt A):2862-72. doi: 10.1016/j.jacc.2013.11.070. Epub 2014 Mar 26. PMID: 24681141
  2. Lp(a)/apo(a) modulate MMP-9 activation and neutrophil cytokines in vivo in inflammation to regulate leukocyte recruitment. Huang M, Gong Y, Grondolsky J, Hoover-Plow J. Am J Pathol. 2014 May;184(5):1503-17. doi: 10.1016/j.ajpath.2014.01.010. Epub 2014 Mar 17. PMID: 24650562
  3. Genetic dissection of quantitative trait Loci for hemostasis and thrombosis on mouse chromosomes 11 and 5 using congenic and subcongenic strains. Hoover-Plow J, Sa Q, Huang M, Grondolsky J. PLoS One. 2013 Oct 17;8(10):e77539. doi: 10.1371/journal.pone.0077539. eCollection 2013. PMID: 24147020
  4. The plasminogen system in regulating stem cell mobilization. Gong Y, Hoover-Plow J. J Biomed Biotechnol. 2012;2012:437920. doi: 10.1155/2012/437920. Epub 2012 Oct 14. Review. PMID: 23118508
  5. Lipoprotein(a) metabolism: potential sites for therapeutic targets. Hoover-Plow J, Huang M. Metabolism. 2013 Apr;62(4):479-91. doi: 10.1016/j.metabol.2012.07.024. Epub 2012 Oct 4. Review. PMID: 23040268
  6. Challenges for heart disease stem cell therapy. Hoover-Plow J, Gong Y. Vasc Health Risk Manag. 2012;8:99-113. doi: 10.2147/VHRM.S25665. Epub 2012 Feb 17. Review. PMID: 22399855
  7. Plasminogen regulates stromal cell-derived factor-1/CXCR4-mediated hematopoietic stem cell mobilization by activation of matrix metalloproteinase-9. Gong Y, Fan Y, Hoover-Plow J. Arterioscler Thromb Vasc Biol. 2011 Sep;31(9):2035-43. doi: 10.1161/ATVBAHA.111.229583. Epub 2011 Jun 30. PMID: 21719761
  8. EMILIN2 (Elastin microfibril interface located protein), potential modifier of thrombosis. Sa Q, Hoover-Plow JL. Thromb J. 2011 May 11;9:9. doi: 10.1186/1477-9560-9-9. PMID: 21569335

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